Bioinformatical identification of key pathways and genes in human hepatocellular carcinoma after CSN5 depletion

Cell Signal. 2018 Sep:49:79-86. doi: 10.1016/j.cellsig.2018.06.002. Epub 2018 Jun 7.

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It has been previously reported that CSN5 depletion is an effective method in human HCC. In the current study, we aimed to uncover gene signatures and key pathways during HCC. Gene expression profiles of GSE26485 were downloaded from GEO database. Totally, 101 differentially expressed genes (DEGs) were up-regulated and 146 ones were down-regulated. Biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed that the DEGs were mainly enriched in regulation of cell growth, oxidation-reduction process, mitotic cytokinesis, negative regulation of macroautophagy, endosome organization, lysosome, biosynthesis of antibiotics, small cell lung cancer and glutathione metabolism and so on (P < 0.05). Protein-protein interaction (PPI) network, Kaplan-Meier, log-rank method, western blot, immunohistochemistry and encyclopedia of DNA elements (ENCODE) analysis showed that CSN5 depletion took effects through down-regulation of SMAD5-related pathways which include EXO1, CENPA and NCAPG, resulting in the inactivation of H3K4me3 and H3K36me3. Those genes represent the promising targets for therapeutic intervention in HCC patients.

Keywords: Bioinformatics analysis; CSN5 depletion; Differentially expressed gene; Hepatocellular carcinoma; SMAD5.

MeSH terms

  • COP9 Signalosome Complex / antagonists & inhibitors
  • COP9 Signalosome Complex / genetics*
  • COP9 Signalosome Complex / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Computational Biology / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Peptide Hydrolases / genetics*
  • Peptide Hydrolases / metabolism
  • Promoter Regions, Genetic
  • Protein Interaction Maps
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcription Factors / genetics
  • Transcriptome

Substances

  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex